Process for the preparation of p-haloalkoxyanilines

ABSTRACT

p-Haloalkoxyanilines are obtained from the corresponding nitrobenzenes by catalytic hydroxylation in the presence of an aqueous acidic reaction medium with the formation of a corresponding aminophenol and reaction of this aminophenol with a halogenated olefin in the presence of water and a catalytic amount of base.

The present invention relates to a process for the preparation ofp-haloalkoxyanilines by catalytic hydroxylation of nitrobenzenes andsubsequent etherification of the resulting OH group by reaction withhalogenated olefins.

p-Haloalkoxyanilines are important intermediates in the preparation ofinsecticidal active ingredients (see for example EP-A 179 022, DE-A 3627 161, EP-A 221 847, EP-A 235 089 and EP-A 343 110). These anilines areusually prepared by reacting halogenated olefins with p-nitrophenolderivatives and subsequently hydrogenating the nitro group (see forexample EP-A 179 022 and EP-A 235 089), by reacting halogenated olefinswith N-acylated p-aminophenols and subsequently cleaving off the N-acylgroup (see for example EP-A 179 022 and EP-A 235 089), by reacting thesalts of p-aminophenols with halogenated olefins (see for example EP-A179 022 and U.S. Pat. No. 4,518,804) or by reacting p-fluoronitrobenzenederivatives with halogenoalcohols (see for example EP-A 235 089) andsubsequently hydrogenating the nitro group catalytically.

A disadvantage of these processes is the number of process steps,particularly if the preparation of the corresponding starting materialsis included. Thus, for example, p-nitrophenol derivatives have to beprepared in a preliminary step by nitration of a phenol, and, followingreaction with halogenated olefins, a further step is required to reducethe nitro group. It is also a great disadvantage that during thenitration, positionally isomeric compounds are also formed which have tobe removed. In the case of the reaction of N-acylated aminophenols, theinsertion and cleaving off of the protective group mean a markedlyincreased process complexity. Preparation of the aminophenol salts bynitration of a phenol and subsequent hydrogenation and salt formation isalso unfavorable in view of the number of process stages and theavailability of the starting materials. This is also true of thereaction of p-fluoronitroaromatic compounds with halogenoalkanols.

The object is thus to find a process for preparing p-haloalkoxyanilineswhich avoids multistage and lengthy reaction sequences and uses readilyavailable starting materials.

A process for preparing p-haloalkoxyanilines of the formula (I) ##STR1##where R¹ is hydrogen, halogen or C₁ -C₄ -halogenoalkyl and

R² to R⁶ are, independently of one another, each hydrogen or halogen, atleast one of the radicals R¹ to R⁴ not being hydrogen, has now beenfound, which comprises converting a nitrobenzene of the formula (II)##STR2## where R⁵ and R⁶ are as defined for formula (I), into a freeaminophenol of the formula (III) ##STR3## where R⁵ and R⁶ are as definedfor formula (I), by catalytic reductive hydroxylation in the presence ofan aqucous-acidic reaction medium, and reacting this aminophenol with ahalogenated olefin of the formula (IV) or (V) ##STR4## where R¹ to R⁴are as defined for formula (I), in the presence of water and a catalyticamount of base.

Halogen, also in halogenoalkyl, is, for example, fluorine, chlorine orbromine.

In preferred meanings, R¹ is C₁ -C₂ -halogenoalkyl, fluorine orchlorine, R² to R⁴ are, independently of one another, hydrogen, fluorineor chlorine, and R⁵ and R⁶ are, independently of one another, hydrogen,fluorine, chlorine or bromine, at least one of the radicals R⁵ and R⁶not being hydrogen.

In particularly preferred meanings, R¹ is perfluoro-C₁ -C₂ -alkyl suchas trifluoromethyl or pentafluoroethyl, R² to R⁴ are, independently ofone another, fluorine or chlorine, and R⁵ and R⁶ are, independently ofone another, hydrogen or chlorine, at least one of the radicals R⁵ andR⁶ being chlorine.

The catalytic reductive hydroxylation can, for example, be carried outwith hydrogen under pressure at elevated temperature and in the presenceof catalysts.

The aqueous acidic reaction medium can be a mixture of water and astrong acid. The strong acid may be inorganic or organic. Examplesinclude sulfuric acid, hydrochloric acid, hydrobromic acid, phosphoricacid, methanesulfonic acid and toluenesulfonic acid. Preference is givento sulfuric acid and hydrochloric acid. The concentration of the acid inthe aqueous acidic reaction mixture may, for example, be from 5 to 30%by weight, preferably from 10 to 20% by weight. The amount of acid can,for example, be from 0.5 to 10 equivalents of acid per equivalent ofnitrobenzene of formula (II) used. This amount is preferably from 1 to 5equivalents, in particular 1.2 to 3 equivalents.

For example, it is possible to use from 5 to 50% by weight, preferablyfrom 10 to 25% by weight, of a nitrobenzene of the formula (II), basedon the aqueous acidic reaction medium.

It is also possible, if desired, to work in the presence of a cosolvent.The cosolvents may be water-miscible organic solvents, for examplewater-miscible cyclic or open-chain ethers, such as tetrahydrofuran,1,4-dioxane, glycol monoalkyl ethers or glycol dialkyl ethers,water-miscible esters or amides, such as ethyl acetate,N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone,lower aliphatic carboxylic acids, such as formic acid, acetic acid orpropionic acid, water-miscible ketones, such as acetone or methyl ethylketone, or water-miscible alcohols, such as methanol, ethanol, propanolor ethylene glycol. Preference is given to methanol, ethanol, ethyleneglycol, ethylene glycol monomethyl ether, ethylene glycol dimethyl etherand 1,4-dioxane. Cosolvents may optionally be used in from 0.05 to 3times, preferably from 0.1 to 1 times, the quantity by weight, based onthe nitrobenzene of the formula (II) used.

In addition to the cosolvent, it is also possible to use awater-insoluble organic solvent in which the nitrobenzene of the formula(II) used is at least partially soluble. Examples are optionally alkyl-and/or halogen-substituted aromatic hydrocarbons, such as benzene,toluene, xylenes, chlorobenzene, dichlorobenzenes, chlorotoluenes ordichlorotoluenes. Toluene and xylenes are preferred. Water-insolubleorganic solvents may optionally be used in from 0.1 to 5 times,preferably from 0.25 to 3 times, the amount by weight, based on thenitrobenzene of the formula (II) used.

It is preferred to work in the presence of a cosolvent and awater-insoluble solvent. Suitable catalysts for the catalytic reductivehydroxylation are, for example, precious metals and precious metalcompounds of the platinum group elements, in particular platinum and/orpalladium and/or their compounds. The catalysts may be supported on asupport material. Suitable support materials are, for example, silicagels, aluminum oxides, zeolites, molecular sieves or charcoals, whosecoating with precious metals or precious metal compounds can, forexample, be from 0.05 to 10% by weight, preferably from 0.1 to 5% byweight. It is possible to use, for example, from 0.001 to 0.3% byweight, preferably from 0.01 to 0.1% by weight, of the catalyst(calculated as metal), based on the nitrobenzene of the formula (II)used.

The catalytic reductive hydroxylation can be carried out, for example,at temperatures of from 50 to 160° C. and pressures of from 1 to 50 bar.Preferred conditions are 60 to 130° C. and 1.2 to 20 bar.

It is advantageous to thoroughly mix the reaction mixture during thehydrogen uptake, for example by using stirrers, lifter agitators orshaker autoclaves.

The reaction mixture which is present after the catalytic reductivehydroxylation is complete can, for example, be worked up by firstlyremoving the catalyst, for example by filtration, then separating offand removing the organic phase, adding a base to the aqueous phase and,for example, filtering the suspension which forms at a pH ofapproximately 5 to 8, washing the filtration residue with water anddrying it. It is also possible to initially add sufficient base to theaqueous phase that the mixture becomes strongly alkaline, and then toremove undesired byproducts by extraction with an organic solvent andthen to adjust the pH to a value in the range from approximately 5 to 8.Suitable bases are, for example, hydroxides and carbonates of alkalimetals and alkaline earth metals, which may also be used as aqueoussolution or suspension. Sodium hydroxide and potassium hydroxide arepreferred.

The free aminophenol of the formula (III) which is obtained during thecatalytic reductive hydroxylation can be used directly in the secondstage of the process according to the invention, the reaction with ahalogenated olefin.

Suitable solvents for this reaction are polar, aprotic solvents, forexample amides, sulfones, nitriles, ketones and ethers. Examples includedimethylformamide, dimethylacetamide, N-methylpyrrolidone,tetramethylenesulfone, acetonitrile, propionitrile, acetone, methylethyl ketone, tetrahydrofuran and 1,4-dioxane. Acetonitrile isparticularly preferred.

Polar, aprotic solvents can, for example, be used in quantities of from200 to 2000 ml, based on 1 mol of aminophenol of the formula (III). Thisamount is preferably from 500 to 1000 ml.

Suitable bases for the reaction of free aminophenols of the formula(III) with halogenated olefins are, for example, hydroxides, carbonatesand hydrogencarbonates of alkali metals and alkaline earth metals,ammonia and organic amines. Examples include sodium carbonate, sodiumhydrogencarbonate, potassium carbonate, cesium carbonate and ammoniumcarbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide andammonium hydroxide, triethylamine and tributylamine, pyridine,4-dimethylaminopyridine and DBU.

Sodium carbonate, triethylamine and alkali metal hydroxides arepreferred.

The base can be used, for example, in an amount which corresponds tofrom 1 to 50% by weight, based on the free aminophenol of the formula(III). It is also possible to meter in the base over the course of thereaction at such a rate that the pH of the reaction mixture alwaysremains in the range from 6 to 9.5.

The reaction mixture for the reaction of a free aminophenol of theformula (III) with a halogenated olefin can, for example, contain from0.5 to 30% by weight of water, which may be added, for example,initially and/or together with the base prior and/or continuously insmall portions during the reaction.

The halogenated olefin is preferably introduced continuously or in smallportions over the course of the reaction, as consumed. Progression ofthe reaction is evident, for example, from the pressure drop,particularly if the reaction is carried out at increased pressure.

It is preferable to introduce the base in the form of an aqueoussolution and the halogenated olefin at the same time, but spatiallyseparate, continuously or in small portions over the course of thereaction.

Suitable temperatures for the reaction of a free aminophenol of theformula (III) with a halogenated olefin are, for example, those in therange from 0 to 120° C. Preferred temperatures are from 5 to 30° C. Thepressure during this reaction can, for example, be in the range from 0.5to 5 bar. It is preferably from 1 to 2.5 bar. p-Haloalkoxyanilines ofthe formula (I) are obtained in particularly good yields and purities ifthe process is carried out at a relatively low temperature and the baseis added simultaneously with the halogenated olefin over the course ofthe reaction and at the rate at which the halogenated olefin isconsumed.

The reaction mixture which is present following the reaction of the freeaminophenol of the formula (III) with the halogenated olefin can, forexample, be worked up by distillation or extraction. Distillation ispreferred. The polar, aprotic solvent may be removed and optionally usedagain, and the prepared p-halogenoalkoxyaniline of the formula (I) canthen be isolated in good yields and purities. Distillation of theproduct is preferably carried out under reduced pressure, for example atfrom 1 to 20 mbar.

The process according to the invention comprises only two reactionsteps, uses readily available starting materials and is not verycomplex.

EXAMPLES Example 1

An enamel autoclave was charged with 480 g of 2,5-dichloronitrobenzene,2000 g of water, 306 g of concentrated sulfuric acid, 85 g of1,2-dimethoxyethane, 4.8 g of 5% by weight platinum-on-charcoal(approximately 60% by weight moist) and 417 g of toluene at roomtemperature. After the system had been rendered inert using nitrogen,hydrogen was introduced with stirring at 105° C. and from 9 to 9.5 bar.After a constant pressure had been achieved, the pressure was releasedand the catalyst removed by filtration while still hot. The aqueousphase was separated off whilst hot, adjusted to a pH of 12 using 50% byweight aqueous sodium hydroxide solution, extracted with 500 ml oftoluene and then adjusted to a pH of 6 using concentrated hydrochloricacid. The suspension formed was filtered off at room temperature andwashed with water. Drying under reduced pressure gave 273.6 g of abrownish-reddish solid which contained 98% of2,5-dichloro-4-aminophenol. This corresponded to a yield of 60.3%.

Example 2

80 g of 2,5-dichloro-4-aminophenol dissolved in 400 ml of acetonitrilewere placed in a reaction vessel fitted with stirrer, reflux condenserand inlet pipe, and then 9 ml of a saturated soda solution were added.Hexafluoropropene was then introduced into the resulting suspension,with vigorous stirring, at the rate of uptake. The reaction was slightlyexothermic, as a result of which the temperature rose from 22° C. to 30°C. After 2 hours, a further 5 ml of the soda solution were added andfurther hexafluoropropene was introduced. After a total of 3 hours thetemperature was 32° C. an almost clear solution had formed and theuptake of hexafluoropropene had ceased. The amount of hexafluoropropeneconsumed was 80 g. The pH of the solution was then 5. The acetonitrilewas then distilled off by raising the temperature and then applying avacuum. In the forerunnings, 380 ml of acetonitrile passed over. After asmall intermediate fraction, 137 g of2-H-hexafluoropropoxy-2,5-dichloroaniline were obtained at 145° C. and20 mbar. The purity (determined by gas chromatography) was 97%. Theprincipal minor component present was 1.5% of a product formed byelimination of hydrogen fluoride. The yield was 90%, based on 100%content of starting material and product.

Example 3

160 g of 2,5-dichloro-4-aminophenol dissolved in 700 ml of acetonitrilewere placed in an autoclave fitted with stirrer, reflux condenser andinlet pipe, and then 10 ml of triethylamine and 10 ml of water wereadded. Hexafluoropropene was introduced, with vigorous stirring, inportions into the resulting mixture at 20° C. The reaction was slightlyexothermic, as a result of which the temperature rose to 25° C. After 5cycles a total of 150 g of hexafluoropropene had been added. After atotal reaction time of 3 hours the reaction mixture was transferred to adistillation apparatus and the acetonitrile was distilled off by raisingthe temperature. In the forerunnings, 684 ml of acetonitrile passedover. After a small intermediate fraction, 275 g of2-H-hexafluoropropoxy-2,5-dichloroaniline were obtained in the boilingrange from 145 to 148° C. and at 18 mbar. The purity of the product(determined by gas chromatography) was 97.2%. The essential minorcomponents were 2.75% of hydrogen fluoride elimination products.Accordingly, the yield was 90.3%, based on aminophenol used, and 83.8%,based on hexafluoropropene.

Example 4 (as comparison)

Example 2 was repeated but using further water instead of acetonitrile.In this way, 2-H-hexafluoropropoxy-2,5-dichloroaniline was obtained in ayield of only 10%.

What is claimed is:
 1. A process for the preparation ofp-haloalkoxyanilines of the formula (I) ##STR5## where R¹ is hydrogen,halogen or C₁ -C₄ -halogenoalkyl andR² to R⁶ are, independently of oneanother, each hydrogen or halogen, at least one of the radicals R¹ to R⁴not being hydrogen,which comprises converting a nitrobenzene of theformula (II) ##STR6## where R⁵ and R⁶ are as defined for formula (I),into a free aminophenol of the formula (III) ##STR7## where R⁵ and R⁶are as defined for formula (I), by catalytic reductive hydroxylation inthe presence of an aqueous-acidic reaction medium, and reacting thisaminophenol with a halogenated olefin of the formula (IV) or (V)##STR8## where R¹ to R⁴ are as defined for formula (I), in the presenceof water and a catalytic amount of base.
 2. A process as claimed inclaim 1, wherein, in the formulae, R¹ is C₁ -C₂ -halogenoalkyl, fluorineor chlorine, R² to R⁴ are, independently of one another, hydrogen,fluorine or chlorine, and R⁵ and R⁶, independently of one another, arehydrogen, fluorine, chlorine or bromine, at least one of the radicals R⁵and R⁶ not being hydrogen.
 3. A process as claimed in claim 1, whereinthe aqueous acidic reaction medium comprises a mixture of water and astrong acid.
 4. A process as claimed in claim 1, wherein theconcentration of the acid in the aqueous acidic reaction mixture is from5 to 30% by weight and the amount of acid is from 0.5 to 10 equivalentsof acid per equivalent of nitrobenzene of the formula (II) used.
 5. Aprocess as claimed in claim 1, wherein the catalytic reductivehydroxylation is also carried out in the presence of a cosolvent whichis a water-miscible organic solvent.
 6. A process as claimed in claim 1,wherein the catalytic reductive hydroxylation is carried out in thepresence of a cosolvent which is a water-miscible organic solvent, andalso in the presence of a water-insoluble organic solvent.
 7. A processas claimed in claim 1, wherein the catalytic reductive hydroxylation iscarried out at from 50 to 160° C. and from 1 to 50 bar.
 8. A process asclaimed in claim 1, wherein the reaction with a halogenated olefin iscarried out in the presence of hydroxides, carbonates orhydrogencarbonates of alkali metal or alkaline earth metals or ammoniaor organic amines.
 9. A process as claimed in claim 1, wherein thereaction with halogenated olefins uses from 1 to 50% by weight of base(based on the free aminophenol of the formula (III)).
 10. A process asclaimed in claim 1, wherein the reaction mixture for the reaction with ahalogenated olefin contains from 0.5 to 30% by weight of water, and theprocess conditions are from 0 to 120° C. and from 0.5 to 5 bar.